Another solstice for CTLA-4

Despite a long-standing reputation for toxicity, CTLA-4 remains a target that drugmakers seem unwilling to abandon. The latest company to place a bet here is Solstice Oncology, a newly-formed private biotech that has licensed Harbour Biomed’s CTLA-4 targeting antibody porustobart outside China in a deal worth over $105m in upfront and near-term payments.

Solstice, which is paying $50m in up-front cash, "over" $50m in equity, and $5m in "near-term cash payments", was incorporated in the UK earlier this month and has yet to disclose any broader pipeline, making porustobart its sole known asset. 

Colorectal

Porustobart arrives at the company with a growing body of clinical evidence. In October, Harbour Biomed reported data from 23 patients with microsatellite-stable metastatic colorectal cancer treated with porustobart in combination with BeOne’s Tevimbra. The combination delivered an overall response rate of 35%, including eight partial responses. 

As with other CTLA-4 agents, however, safety remains a concern, with treatment-related serious adverse events were observed in 38% of patients.

Still, there's plenty of activity in this arena. According to OncologyPipeline, porustobart is one of at least 24 monoclonal antibodies targeting CTLA-4 currently in clinical development, highlighting continued industry interest in the mechanism despite its risks.

Beyond monoclonal antibodies, companies are also pursuing bispecific approaches, but these efforts have also encountered setbacks.

MacroGenics

Last November, MacroGenics discontinued development of its PD-1 x CTLA-4 bispecific antibody lorigerlimab in prostate cancer following disappointing results in the phase 2 Lorikeet trial. And on Monday, the company disclosed that the US FDA has placed a partial clinical hold on the phase 2 Linnet study evaluating lorigerlimab in gynaecologic cancers. 

The decision followed four grade 4 adverse events among the 41 patients enrolled to date. These included thrombocytopenia (two cases), myocarditis (one case), and neutropenia with concurrent septic shock (one case) that resulted in the patient's death. 

Data from the Linnet trial had been expected in mid-2026, but lorigerlimab's future now looks even dimmer.